MK-7625A Plus Metronidazole Versus Meropenem in Pediatric Participants With Complicated Intra-Abdominal Infection (cIAI) (MK-7625A-035)

NCT03217136 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: 7625A-035MK-7625A-0352016-004820-41
• Study Type: interventional
• Target: 94
• Locations: 12 countries
• Sites: 50

Brief Summary

This study aims to evaluate the safety and tolerability of MK-7625A (ceftolozane/tazobactam) plus metronidazole, compared with that of meropenem in pediatric participants with cIAI.

Conditions

Complicated Intra-Abdominal Infection

Outcome Measures

Primary Outcomes (2)

• Number of Participants Experiencing ≥1 Adverse Events (AEs)

  An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE is presented.

  Up to approximately 75 days

• Number of Participants Who Discontinued Study Therapy Due to AE(s)

  An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study treatment due to an AE is presented.

  Up to approximately 18 days

Secondary Outcomes (4)

• Percentage of Participants With a Clinical Response of "Cure" at the End of Treatment (EOT) Visit

  Up to approximately 27 days

• Percentage of Participants With a Clinical Response of "Cure" at the Test of Cure (TOC) Visit

  Up to approximately 39 days

• Percentage of Participants With Microbiological Eradication at the EOT Visit

  Up to approximately 27 days

• Percentage of Participants With Microbiological Eradication at the TOC Visit

  Up to approximately 39 days

Study Arms (2)

Ceftolozane/Tazobactam + Metronidazole

EXPERIMENTAL

Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose), plus metronidazole 10 mg/kg (maximum 1.5 g/day) administered intravenously (IV) every 8 to 12 hours for 5 to 14 days.

Drug: Ceftolozane/Tazobactam; Drug: Metronidazole

Meropenem + Placebo for Metronidazole

ACTIVE COMPARATOR

Meropenem 20 mg/kg (maximum 1 g/dose) plus placebo for Metronidazole administered IV every 8 hours for 5 to 14 days.

Drug: Meropenem; Drug: Placebo for Metronidazole

Interventions

Ceftolozane/Tazobactam DRUG

Ceftolozane 20 mg/kg (maximum 1 g) and tazobactam 10 mg/kg (maximum 0.5 g/dose) administered IV every 8 hours for between 5 to 14 days.

Also known as: MK-7625A

Ceftolozane/Tazobactam + Metronidazole

Metronidazole DRUG

Metronidazole 10 mg/kg (maximum 1.5 g/day) administered IV every 8 hours for between 5 to 14 days. Participants ≤ 28 days old, start with a loading dose of 15 mg/kg; then if ≤ 2 kg are dosed 7.5 mg/kg/ every 12 hours; or if \> 2 kg are dosed 10 mg/kg every 8 hours.

Ceftolozane/Tazobactam + Metronidazole

Meropenem DRUG

Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for between 5 to 14 days.

Also known as: MERREM

Meropenem + Placebo for Metronidazole

Placebo for Metronidazole DRUG

Placebo for metronidazole administered IV every 8 hours for between 5 to 14 days.

Meropenem + Placebo for Metronidazole

Eligibility Criteria

• Age: 7 Days - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Has a legally acceptable representative who provides documented informed consent/assent for the trial.
• Aged from birth (defined as \>32 weeks gestational age and ≥7 days postnatal) to \<18 years of age.
• Require IV antibacterial therapy for the treatment of presumed or documented cIAI.
• Has an operative procedure for the current diagnosis and management of cIAI planned or completed within 24 hours of the first dose of an antibacterial drug. Note: Participants with a diagnosis of necrotizing enterocolitis are exempt and not required to have surgery planned or completed in order to be eligible.
• Has in compliance baseline intra-abdominal specimen collection.
• Is not of reproductive potential; but if of reproductive potential agrees to avoid becoming pregnant or impregnating a partner during screening, while receiving study treatment and for at least 30 days after the last dose of study treatment.
• Female of reproductive potential is not pregnant, and not planning to become pregnant within 30 days of the last day of treatment administration; and is nonlactating.

You may not qualify if:

• Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 30 days prior to the first dose of study treatment in this current trial.
• Has previously participated in any trial of ceftolozane or ceftolozane/tazobactam or has enrolled previously in the current trial and been discontinued.
• Has a history of any moderate or severe hypersensitivity (e.g, anaphylaxis), allergic reaction, or other contraindication to any of the following: β-lactam antibiotics (e.g, penicillins, cephalosporins, and carbapenems), β-lactamase inhibitors (e.g, tazobactam, sulbactam, clavulanic acid, avibactam), or metronidazole.
• Has an IAI within the past 1 year prior to randomization known to be caused by a pathogen resistant to either IV study treatment.
• Has a concomitant infection at the time of randomization that requires non-study systemic antibacterial therapy in addition to IV study treatment or oral step-down therapy.
• Has received potentially therapeutic antibacterial therapy for a duration more than 24 hours during the 48 hours preceding the first dose of study treatment, unless is considered to be failing antibiotic therapy for cIAI.
• Has any of the following: a) intractable cIAI that the investigator anticipates would require more than 14 days of study treatment; b) abdominal wall abscess; c) small bowel obstruction; d) ischemic bowel disease without perforation; e) traumatic bowel perforation with surgery within 12 hours of perforation; f) perforation of gastroduodenal ulcers requiring surgery within 24 hours of perforation; g) suspected uncomplicated intra-abdominal infection (e.g, cholecystitis without rupture or extension beyond the gallbladder wall); h) acute suppurative cholangitis; i) infected necrotizing pancreatitis; j) pancreatic abscess.
• Has moderate or severe impairment of renal function.
• Has a seizure disorder or is anticipated to be treated with divalproex sodium or valproic acid during the course of study treatment.
• Is receiving, or is expected to receive, any prohibited medications.
• Has any rapidly progressing disease or immediately life-threatening illness, including acute hepatic failure, respiratory failure, or septic shock.
• Has an immunocompromising condition.
• Has a history of malignancy ≤5 years prior to signing informed consent.
• Is planning to receive suppressive/prophylactic antibiotics with gram-negative activity after completion of study treatment.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (50)

Children's Hospital - Los Angeles ( Site 2508)

Los Angeles, California, 90027, United States

Location

Children's Hospital of Orange County ( Site 2502)

Orange, California, 92868, United States

Location

Rady Children's Hospital-San Diego ( Site 2505)

San Diego, California, 92123, United States

Location

Baptist Medical Center/Wolfson Children's Hospital ( Site 2521)

Jacksonville, Florida, 32207, United States

Location

Tufts Medical Center-Floating Hospital for Children ( Site 2516)

Boston, Massachusetts, 02111, United States

Location

St. Louis Children's Hospital ( Site 2511)

St Louis, Missouri, 63110, United States

Location

SUNY Upstate Medical University Hospital ( Site 2509)

Syracuse, New York, 13210, United States

Location

Primary Children's Hospital ( Site 2500)

Salt Lake City, Utah, 84113, United States

Location

Seattle Childrens Hospital ( Site 2510)

Seattle, Washington, 98105, United States

Location

Hospital Pequeno Principe ( Site 0200)

Curitiba, Paraná, 80250-060, Brazil

Location

Inst de Medicina Integral Professor Fernando Figueira- IMIP ( Site 0201)

Recife, Pernambuco, 50070-550, Brazil

Location

Hospital Tacchini ( Site 0203)

Bento Gonçalves, Rio Grande do Sul, 95700-068, Brazil

Location

PTE AOK Klinikai Kozpont ( Site 0805)

Pécs, Baranya, 7623, Hungary

Location

SzSzBMK es Egyetemi Oktatokorhaz Josa Andras Oktatokorhaz ( Site 0804)

Nyíregyháza, Szabolcs-Szatmár-Bereg, 4400, Hungary

Location

Semmelweis Egyetem ( Site 0807)

Budapest, 1083, Hungary

Location

Heim Pal Orszagos Gyermekgyogyaszati Intezet ( Site 0806)

Budapest, 1089, Hungary

Location

Debreceni Egyetem Klinikai Kozpont ( Site 0801)

Debrecen, 4032, Hungary

Location

SZTE Szent-Gyorgyi Albert Klinikai Kozpont ( Site 0802)

Szeged, 6720, Hungary

Location

Hospital of Lithuanian University of Health Sciences Kaunas ( Site 1001)

Kaunas, 50161, Lithuania

Location

Klaipedos Vaiku Ligonine ( Site 1000)

Klaipėda, 92140, Lithuania

Location

Vaiku Ligonine VU ligonines Santariskiu kliniku filialas ( Site 1002)

Vilnius, 08406, Lithuania

Location

Universiti Kebangsaan Malaya Medical Centre ( Site 1101)

Cheras, Johor, 56000, Malaysia

Location

Hospital Pulau Pinang ( Site 1102)

George Town, Pulau Pinang, 10990, Malaysia

Location

University Malaya Medical Centre. ( Site 1100)

Kuala Lumpur, 59100, Malaysia

Location

Hospital del Nino y Adolescente Morelense ( Site 1204)

Emiliano Zapata, Morelos, 62765, Mexico

Location

Instituto Tecnologico y de Estudios Superiores de Monterrey ( Site 1203)

Monterrey, Nuevo León, 64710, Mexico

Location

Instituto Nacional de Pediatria ( Site 1201)

Mexico City, 04530, Mexico

Location

Hospital Infantil de Mexico Federico Gomez ( Site 1202)

Mexico City, 06720, Mexico

Location

Spit. Cl. de Urg. Copii Cluj Napoca ( Site 1703)

Cluj-Napoca, Cluj, 400370, Romania

Location

Spitalul Clinic de Urgenta pentru Copii "Louis Turcanu" Timi ( Site 1701)

Timișoara, Timiș County, 300011, Romania

Location

Chelyabinsk Regional Children Clinical Hospital ( Site 1802)

Chelyabinsk, Chelyabinsk Oblast, 454087, Russia

Location

Smolensk Regional Clinical Hospital ( Site 1800)

Smolensk, Smolensk Oblast, 214018, Russia

Location

Stavropol Regional Pediatric Clinical Hospital ( Site 1805)

Stavropol, Stavropol Kray, 355029, Russia

Location

Regional Childrens Clinical Hospital ( Site 1809)

Vologda, Vologda Oblast, 160022, Russia

Location

Molotlegi Street ( Site 1901)

Pretoria, Gauteng, 0208, South Africa

Location

Red Cross War Memorial Children's Hospital ( Site 1902)

Cape Town, Western Cape, 7700, South Africa

Location

Hospital Clinico Universitario de Santiago ( Site 2001)

Santiago de Compostela, A Coruña [La Coruña], 15706, Spain

Location

Institut Catala d Oncologia Hospital Germans Trias i Pujol ( Site 2004)

Badalona, Barcelona, 08916, Spain

Location

Hospital Universitario Sant Joan de Deu ( Site 2000)

Esplugues de Llobregat, Barcelona, 08950, Spain

Location

Hospital Universitario la Fe ( Site 2003)

Valencia, Valenciana, Comunitat, 46026, Spain

Location

Cukurova Uni Tip Fak Cocuk Saglıgı ve Hasta ABD ( Site 2200)

Adana, 01330, Turkey (Türkiye)

Location

Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 2201)

Ankara, 06230, Turkey (Türkiye)

Location

Eskisehir Osmangazi Unv. Tip Fakultesi ( Site 2202)

Eskişehir, 26480, Turkey (Türkiye)

Location

SBU Sariyer Hamidiye Etfal Egitim ve Arastirma Hastanesi ( Site 2203)

Istanbul, 34453, Turkey (Türkiye)

Location

SI Dnipropetrovsk Regional Children Clinical Hospital DOR ( Site 2452)

Dnipro, Dnipropetrovsk Oblast, 49100, Ukraine

Location

PI Kryvorizka city clinical hospital 8 ( Site 2458)

Kryvyy Rig, Dnipropetrovsk Oblast, 50082, Ukraine

Location

Ivano-Frankivsk Regional Children Clinical Hospital ( Site 2461)

Ivano-Frankivsk, Ivano-Frankivsk Oblast, 76014, Ukraine

Location

National Children Specialised Hospital OHMADYT MOH Ukraine ( Site 2459)

Kyiv, Kyivska Oblast, 01135, Ukraine

Location

Municipal Institution City Children s Clinical Hospital of Poltava City Council ( Site 2454)

Poltava, Poltava Oblast, 36004, Ukraine

Location

Vinnytsya Regional Children Clinical Hospital ( Site 2463)

Vinnytsia, Vinnytsia Oblast, 21029, Ukraine

Location

Related Publications (1)

• Jackson CA, Newland J, Dementieva N, Lonchar J, Su FH, Huntington JA, Bensaci M, Popejoy MW, Johnson MG, De Anda C, Rhee EG, Bruno CJ. Safety and Efficacy of Ceftolozane/Tazobactam Plus Metronidazole Versus Meropenem From a Phase 2, Randomized Clinical Trial in Pediatric Participants With Complicated Intra-abdominal Infection. Pediatr Infect Dis J. 2023 Jul 1;42(7):557-563. doi: 10.1097/INF.0000000000003911. Epub 2023 Mar 29.

  PMID: 37000942 RESULT

MeSH Terms

Interventions

ceftolozane, tazobactam drug combination; Metronidazole; Meropenem

Intervention Hierarchy (Ancestors)

Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2017
• First Posted: July 13, 2017
• Study Start: April 3, 2018
• Primary Completion: March 16, 2020
• Study Completion: March 16, 2020
• Last Updated: May 6, 2023
• Results First Posted: December 21, 2021

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share

Locations

ES (4); TU (4); RO (2); US (9); BR (3); LI (3); ME (4); ZA (2); HU (6); MY (3); UA (6); RU (4)